- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01869010
Severe Impairment of Solute-Free Water Clearance in Patients With HIV Infection
The objective of the present study is to analyze the overall tubular function, and in particular that from the proximal tubule and the thick ascending loop of Henle (TALH) in patients with HIV infection receiving or not tenofovir-containing antiretroviral treatment in comparison with seronegative controls, by applying a validated tubular physiological test known as "Low sodium infusion test".
Hypothesis is that patients with HIV infection and normal renal function will show subclinical tubular abnormalities compared with seronegative controls
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Renal disease is a well recognized complication among patients with HIV infection. Either viral infection itself and the use of some antiretroviral drugs contribute to this serious non AIDS-defining condition that may affect both the glomeruli and the renal tubules.
The thick ascending loop of Henle constitutes the main location for free-water clearance determining kidney´s ability to concentrate and dilute urine in a direct and indirect fashion, respectively.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Caba
-
Buenos Aires, Caba, Argentina, 1181
- Hospital Italiano de Buenos Aires - Infectious Diseases Section
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Inclusion criteria are as follows: adult patients (≥18 years old) with confirmed chronic HIV-1 infection who agreed to provide written informed consent. Patients under antiretroviral treatment must had a stable regimen for over six months and undetectable (<50 copies/ml) viral load for at least three months. At study entry all selected patients were confirmed as having normal physical examination, routine clinical laboratory including urinalysis, as well as renal and cardiac ultrasound.
Exclusion Criteria:
- Exclusion criteria include patients with acute HIV infection (< 6 months of disease), personal history of nephropathy, plasma creatinine ≥1.3 mg/dl, Glomerular filtration rate ≤60ml/min/1.73 m² (as determined by Modification of Diet in renal Disease formula), presence of glucosuria/proteinuria (measured in spot urine sample), prior heart failure, concurrent opportunistic infection, chronic active hepatitis B or C, and use of potentially nephrotoxic agents in the prior week before the test (e.g diuretics, angiotensin converting enzyme antagonists, Angiotensin II receptor antagonists or non-steroidal anti-inflammatory agents).
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
HIV Tenofovir
|
This test is based on the exploration of the tubular response to an acute fluid load.
After overnight fast, all participants received twenty cc/Kg of mineralized water per os and two liters of intravenous hypotonic solution (0.66%) infused in two hours.
Three blood samples are drawn (at 0, 60 and 120 minutes) and also urine samples are collected from each person at baseline and at 30 (±5) minutes intervals during the whole test.
From the obtained blood and urine samples creatinine and osmolarity are measured, and then from the data corresponding to the most hypotonic urine sample (maximum dilution) and its corresponding blood sample three renal physiological parameters (proximal sodium clearance, free water clearance, sodium TALH reabsorption) are analyzed.
Since patient inclusion follow up period is one month
|
HIV No tenofovir
|
This test is based on the exploration of the tubular response to an acute fluid load.
After overnight fast, all participants received twenty cc/Kg of mineralized water per os and two liters of intravenous hypotonic solution (0.66%) infused in two hours.
Three blood samples are drawn (at 0, 60 and 120 minutes) and also urine samples are collected from each person at baseline and at 30 (±5) minutes intervals during the whole test.
From the obtained blood and urine samples creatinine and osmolarity are measured, and then from the data corresponding to the most hypotonic urine sample (maximum dilution) and its corresponding blood sample three renal physiological parameters (proximal sodium clearance, free water clearance, sodium TALH reabsorption) are analyzed.
Since patient inclusion follow up period is one month
|
Seronegative controls
|
This test is based on the exploration of the tubular response to an acute fluid load.
After overnight fast, all participants received twenty cc/Kg of mineralized water per os and two liters of intravenous hypotonic solution (0.66%) infused in two hours.
Three blood samples are drawn (at 0, 60 and 120 minutes) and also urine samples are collected from each person at baseline and at 30 (±5) minutes intervals during the whole test.
From the obtained blood and urine samples creatinine and osmolarity are measured, and then from the data corresponding to the most hypotonic urine sample (maximum dilution) and its corresponding blood sample three renal physiological parameters (proximal sodium clearance, free water clearance, sodium TALH reabsorption) are analyzed.
Since patient inclusion follow up period is one month
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Free Water Clearance
Time Frame: 1 month
|
Low sodium water overload
|
1 month
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Urine osmolarity
Time Frame: one month
|
one month
|
Collaborators and Investigators
Investigators
- Principal Investigator: Waldo H Belloso, MD, Hospital Italiano de Buenos Aires
Publications and helpful links
General Publications
- Estrella MM, Fine DM, Atta MG. Recent developments in HIV-related kidney disease. HIV Ther. 2010 Sep;4(5):589-603. doi: 10.2217/hiv.10.42.
- Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004 Sep 23;351(13):1296-305. doi: 10.1056/NEJMoa041031. Erratum In: N Engl J Med. 2008;18(4):4.
- Phair J, Palella F. Renal disease in HIV-infected individuals. Curr Opin HIV AIDS. 2011 Jul;6(4):285-9. doi: 10.1097/COH.0b013e3283476bc3.
- Mathew G, Knaus SJ. Acquired Fanconi's syndrome associated with tenofovir therapy. J Gen Intern Med. 2006 Nov;21(11):C3-5. doi: 10.1111/j.1525-1497.2006.00518.x.
- Fernandez-Fernandez B, Montoya-Ferrer A, Sanz AB, Sanchez-Nino MD, Izquierdo MC, Poveda J, Sainz-Prestel V, Ortiz-Martin N, Parra-Rodriguez A, Selgas R, Ruiz-Ortega M, Egido J, Ortiz A. Tenofovir nephrotoxicity: 2011 update. AIDS Res Treat. 2011;2011:354908. doi: 10.1155/2011/354908. Epub 2011 Jun 7.
- Rodriguez-Novoa S, Alvarez E, Labarga P, Soriano V. Renal toxicity associated with tenofovir use. Expert Opin Drug Saf. 2010 Jul;9(4):545-59. doi: 10.1517/14740331003627458.
- Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis. 2010 Sep 1;51(5):496-505. doi: 10.1086/655681.
- Choi AI, Li Y, Deeks SG, Grunfeld C, Volberding PA, Shlipak MG. Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons. Circulation. 2010 Feb 9;121(5):651-8. doi: 10.1161/CIRCULATIONAHA.109.898585. Epub 2010 Jan 25.
- Gupta SK, Smurzynski M, Franceschini N, Bosch RJ, Szczech LA, Kalayjian RC; AIDS Clinical Trials Group Longitudinal Linked Randomized Trials Study Team. The effects of HIV type-1 viral suppression and non-viral factors on quantitative proteinuria in the highly active antiretroviral therapy era. Antivir Ther. 2009;14(4):543-9.
- Kalayjian RC. Kidney Disease in HIV-Infected Persons. Curr Infect Dis Rep. 2012 Feb;14(1):83-90. doi: 10.1007/s11908-011-0228-2.
- Kalayjian RC. Renal issues in HIV infection. Curr HIV/AIDS Rep. 2011 Sep;8(3):164-71. doi: 10.1007/s11904-011-0080-x.
- Szczech LA. Renal dysfunction and tenofovir toxicity in HIV-infected patients. Top HIV Med. 2008 Oct-Nov;16(4):122-6.
- Vrouenraets SM, Fux CA, Wit FW, Garcia EF, Furrer H, Brinkman K, Hoek FJ, Abeling NG, Krediet RT, Reiss P; Prepare Study Group. Persistent decline in estimated but not measured glomerular filtration rate on tenofovir may reflect tubular rather than glomerular toxicity. AIDS. 2011 Nov 13;25(17):2149-55. doi: 10.1097/QAD.0b013e32834bba87.
- Hall AM, Edwards SG, Lapsley M, Connolly JO, Chetty K, O'Farrell S, Unwin RJ, Williams IG. Subclinical tubular injury in HIV-infected individuals on antiretroviral therapy: a cross-sectional analysis. Am J Kidney Dis. 2009 Dec;54(6):1034-42. doi: 10.1053/j.ajkd.2009.07.012. Epub 2009 Sep 23.
- Labarga P, Barreiro P, Martin-Carbonero L, Rodriguez-Novoa S, Solera C, Medrano J, Rivas P, Albalater M, Blanco F, Moreno V, Vispo E, Soriano V. Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir. AIDS. 2009 Mar 27;23(6):689-96. doi: 10.1097/QAD.0b013e3283262a64.
- Chaimovitz C, Levi J, Better OS, Oslander L, Benderli A. Studies on the site of renal salt loss in a patient with Bartter's syndrome. Pediatr Res. 1973 Feb;7(2):89-94. doi: 10.1203/00006450-197302000-00004. No abstract available.
- Tabernero Romo JM, Rodriguez Commes JL, Macias Nunez JF, Bondia Roman A, Corbacho Becerra L, Juanes Gonzalez A, de Castro del Pozo S. [Free erythropoietic protoporphyrins in chronic renal insufficiency]. Rev Clin Esp. 1978 Jul;150(1-2):31-4. No abstract available. Spanish.
- Musso CG, Macias-Nunez JF. Dysfunction of the thick loop of Henle and senescence: from molecular biology to clinical geriatrics. Int Urol Nephrol. 2011 Mar;43(1):249-52. doi: 10.1007/s11255-010-9783-y. Epub 2010 Nov 12.
- Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA, Tashima KT, Roland M, Franceschini N, Palella FJ, Lennox JL, Klotman PE, Nachman SA, Hall SD, Szczech LA. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005 Jun 1;40(11):1559-85. doi: 10.1086/430257. Epub 2005 Apr 22. No abstract available.
- Maggi P, Montinaro V, Bellacosa C, Pietanza S, Volpe A, Graziano G, Strippoli GF, Angarano G. Early markers of tubular dysfunction in antiretroviral-experienced HIV-infected patients treated with tenofovir versus abacavir. AIDS Patient Care STDS. 2012 Jan;26(1):5-11. doi: 10.1089/apc.2011.0185. Epub 2011 Dec 2.
- Menon MC, Garcha AS, Khanna A. The management of hyponatremia in HIV disease. J Nephrol. 2013 Jan-Feb;26(1):61-72. doi: 10.5301/jn.5000168.
- Vitting KE, Gardenswartz MH, Zabetakis PM, Tapper ML, Gleim GW, Agrawal M, Michelis MF. Frequency of hyponatremia and nonosmolar vasopressin release in the acquired immunodeficiency syndrome. JAMA. 1990 Feb 16;263(7):973-8.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- RNA Virus Infections
- Virus Diseases
- Blood-Borne Infections
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Disease Attributes
- Slow Virus Diseases
- HIV Infections
- Infections
- Communicable Diseases
- Acquired Immunodeficiency Syndrome
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
Other Study ID Numbers
- HIBA 1237
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV Infection
-
Erasmus Medical CenterNot yet recruitingHIV Infections | Hiv | HIV-1-infection | HIV I InfectionNetherlands
-
Sociedad Andaluza de Enfermedades InfecciosasConsejeria de Salud. Junta de Andalucia. SpainCompletedHIV Infection | HIV-1 InfectionSpain
-
Beckman Coulter, Inc.CompletedHIV I Infection | HIV-2 InfectionFrance
-
Allegheny Singer Research Institute (also known...Active, not recruitingHIV Infections | HIV-1-infection | HIV I InfectionUnited States
-
Rockefeller UniversityCompletedHIV Infection | Healthy Volunteers | HIV-1 InfectionUnited States
-
Erasmus Medical CenterRecruitingHIV Infections | HIV-1-infection | HIV-2 InfectionNetherlands
-
Erasmus Medical CenterActive, not recruitingHIV Infections | HIV-1-infection | HIV-2 InfectionNetherlands
-
AIDS Healthcare FoundationUniversity of California, Los AngelesCompleted
-
Merck Sharp & Dohme LLCCompleted
-
National Institute of Allergy and Infectious Diseases...CompletedHIV-1 Infection | HIV Antibodies | Neutralizing Antibody | Viral Load | Monoclonal AntibodyUnited States
Clinical Trials on Low sodium water overload in HIV tenofovir, HIV no tenofovir and seronegative controls
-
French National Agency for Research on AIDS and...Gilead Sciences; PharmassetTerminatedHBe Negative Chronic Hepatitis B | Hepatitis B Viral InfectionFrance
-
Duke UniversityThe Emmes Company, LLCRecruitingHIV Infections | Lactating Women on Select DOI | Breastmilk Fed Infants of Mothers on Select DOISouth Africa
-
Hospital Clinic of BarcelonaCompleted
-
University of Yaounde 1Institut National de la Santé Et de la Recherche Médicale, FranceUnknown
-
University of North Carolina, Chapel HillNational Institute on Drug Abuse (NIDA); National Institute of Mental Health...Completed
-
Janssen Sciences Ireland UCCompleted
-
Gilead SciencesCompletedChronic Hepatitis BUnited States, Canada, Spain, Singapore, Turkey, Germany, France, Taiwan, Greece, Italy, Poland
-
HIV Prevention Trials NetworkGilead SciencesActive, not recruitingHIV PreventionUnited States, Brazil
-
Boehringer IngelheimCompleted
-
Johns Hopkins UniversityNational Institute of Allergy and Infectious Diseases (NIAID); CONRADCompletedHIV/AIDS | HIV PreventionUnited States